| Objective:Germinal matrix-intraventricular hemorrhage(GM-IVH) remains a major cause of acquired brain injury in preterm infants, accounts for at least more than 80% of the neonatal intracranial hemorrhage. According to the report in the literature, premature babies with the gestational age(GM) less 32 week or(and) birth weight less 1500 g, the incidence of IVH was 20% to 40%. The incidence of GM-IVH in preterm infants was significantly higher in our country than in developed countries, it was about 56.6%, The incidence of severe hemorrhage was 16.3%. 35% of the survivors would left behind chronic neurological disorders. Magnetic resonance imaging of brain in the survivors included cerebral white matter focal necrosis, cystic-cavity formation or diffuse periventricular neucomalacia, post-hemorrhagic hydrocephalus, ventriculomegaly, brain atrophy and so on. Histopathological basis is hypomyelination. Currently, there is no better strategy to prevent hypomyelination and the neurological disabilities due to IVH among the survivors. According to the literature reports, trauma or inflammation diseases affected the expression of iodine enzyme in the nervous system, which affected the central nervous system in the biological function of thyroid hormone. A large number of studies have confirmed that thyroid hormone could promote glial progenitor cells mature, myelination, alleviate symptoms of central nervous diseases. Whether thyroid hormone supplementation woluld enhance neurol repairrment in preterm newborns with GM-IVH? There is less related reports. This animal experiment is to test the proteins expressed in thyroid hormone signaling pathways, do thyroid hormone intervention rabbit with GM-IVH impact the expression of related proteins in thyroid hormone signaling pathways? and do thyroid hormone will influence of the maturation of oligodendrocytes? The purpose of this study wants to answer whether thyroid hormone can enhance the expression of myelin basic protein(MBP) in the central nervous system, and hopes to provide some new ideas for the treatment of premature infants with GM-IVH.Methods:1 Premature rabbits were born by cesarean section and given incubated, milk powder feeding after born. Then the premature rabbits were randomly divided into three groups, nomal group, GM-IVH model group(GM-IVH group) and model group treated with thyroid hormone(GM-IVH+T3 group), and each group had twenty premature rabbits. With reference to the method of intra-peritoneal injection which induces GM-IVH. Model preparation method was as follows: the premature rabbits in GM-IVH group and GM-VIH+T3 group were administered 50% glycerol(10ml/kg) at 3hour of age after inducing GM-IVH. After cerebral ultrasound screening at 24 hour of age, the premature rabbits with GM-IVH in GM-IVH+T3 group were given intra-peritoneal injection of triiodothyronin(T3)(20μg/kg·d); the premature rabbits without GM-IVH in normal group were given intra-peritoneal injection of the same dose of saline.2 Within each group, premature rabbits were randomly divided into three sub-groups(3 days,7 days and14 days after GM-IVH). All the premature rabbits were given euthanasia and then the peri-ventricular zone tissue were quickly separated on ice. One part was put in-80 refrigerator, ℃ the other part was immersed in 4% paraformaldehyde solution, for the use of western blot and immunohistochemical experiment.3 The expression of type 2 iodothyronine deiodinase(D2) and type 3 iodothyronine deiodinase(D3) of periventricular zone tissue were detected by western blot method and the expression of myelin basic protein(MBP) were detected by immunohistochemical method.4 Statistical analysis SPSS13.0 statistics software and Microsoft Excel 2003 were used to carry on statistics processing. Measurement data was performed with mean±standard deviation. If the data are homogeneity of variance,the comparison between or among groups were performed with LSD. If they do not meet the homogeneity of variance, use rank sum. P-value<0.05(double side) had statistical significance, highly significant when P-value<0.01.Results:1 Successfully copied the model of premature rabbit with GM-IVH. We performed a cesarean section to deliver the pups prematurely at embryonic day(E) E29(full-term, E32). The head ultrasound screening、specimen、HE staining showed the intra-ventricular hemorrhage in preterm rabbits.2 The expression of deiodinase of brain tissue: from 3 to14 days after birth, the expression of D2 in the normal group increased gradually, the expression of D2 in the GM-IVH group reduced gradually, meanwhile the expression of D2 in GM-IVH group was lower than that in the normal group at different time, and difference reached statistical significance(P<0.01); from 3 to 14 days after birth, the expression of D3 in the normal group decreased gradually, the expression of D3 in the GM-IVH group increased gradually, meanwhile the expression of D3 in GM-IVH group are higher than that in the normal group at different time, and difference reached statistical significance(P < 0.01);In GM-IVH+T3 group, the expression of D2 at 7 or 14 days was significantly higher than that in GM-IVH group, but lower than that in normal group, all had significant difference(P-value<0.01). In GM-IVH+T3 group, the expression of D3 was significantly lower than that in GM-IVH group, but higher than that in normal group, all had significant difference(P-value<0.01);3 The expression of MBP in brain tissue: The expression of MBP was decreased gradually in the model group, but lower than that in the normal group at different time, the difference was significant(P-value<0.01); In GM-VIH+T3 group, the expression of MBP was higher than that in model group at 14 days after born, and the difference was significant(P-value<0.01),but at 3 or 7 days after born,there was no difference between GM-IVH group and GM-IVH+T3 group(P-value>0.05).Conclusions: In the premature rabbit with the GM-IVH, the expression of D2 were reduced, the expression of D3 were increased, the expression of MBP were reduced as time changed markedly.The intervention of thyroid hormone improved expression of D2, reduced the expression of D3, and increased the expression of MBP to a certain extent. When premature rabbits suffered from GM-IVH, the expression level of deiodenase was obviously affected, which affect local tissue low thyroid hormone levels leading to hypomyelination. Given that TH treatment would promote neurological recovery in premature rabbit with GM-IVH, TH treatment might improve the neuro-developmental outcome of preterm infants with GM-IVH. |
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